Abstract
When ingesting a drug on its own or injecting it directly into tissue, its concentration increases immediately within the body, which often exacerbates the side effects and increases its toxicity. To solve this problem, we synthesized the thermally reactive polymer poly(N-isopropylacrylamide) (PNIPAM) using reversible addition–fragmentation chain transfer (RAFT) polymerization and prepared nanocarriers by binding PNIPAM to gold nanorods (GRs), with the anticancer agent doxorubicin (DOX) used as a model drug. PNIPAM changes from hydrophilic to hydrophobic at temperatures above its lower critical solution temperature, which represents a coil-to-globule volume phase transition. Because GRs absorb near-infrared (NIR) laser light and emit energy, PNIPAM aggregation occurs when the synthesized PNIPAM/GR are subjected to an NIR laser, and the temperature of the GRs rises. Using this principle, DOX was combined with the PNIPAM/GR complex, and the resulting anticancer effects with and without laser treatment were observed in Hela and MDA-MB-231 cells. In our proposed complex, the GR binding rate of PNIPAM reached 20% and the DOX binding rate reached 15%. The release profile of the drug following laser irradiation was determined using a drug release test and confocal microscopy imaging. It was subsequently confirmed that the release of the drug is higher at higher temperatures, especially with laser treatment. The proposed combination of temperature-reactive polymers and gold nanostructures shows promise for future research into controlled drug release.
Highlights
Surgery, radiation therapy, and chemotherapy are the most common treatments for cancer worldwide, but chemotherapy in particular has various side effects, including strong cytotoxicity caused by the drugs attacking normal cells [1,2,3]
PNIPAM is hydrophilic at temperatures below the lower critical solution temperature (LCST), but aggregation occurs at temperatures above the LCST when PNIPAM becomes hydrophobic [14,15]
A two-neck flask containing the synthesized PNIPAM solution, which corresponds to the termination of reversible addition–fragmentation chain transfer (RAFT) polymerization, was placed in ice and 10 mL of n-hexane was stored in ice in a 40–60 mL beaker to make it cold
Summary
Radiation therapy, and chemotherapy are the most common treatments for cancer worldwide, but chemotherapy in particular has various side effects, including strong cytotoxicity caused by the drugs attacking normal cells [1,2,3]. To control the release rate, nanocarriers that release the drug when exposed to either internal or external stimuli have been proposed. A number of these nanocarriers are synthesized using stimuli-reactive polymers [9], especially poly(N-isopropylacrylamide) (PNIPAM), which is a well-known temperature-reactive polymer [10,11]. Temperature-reactive polymers all have a lower critical solution temperature (LCST), and that of PNIPAM ranges from 30 to 45 ◦C [12,13]. PNIPAM undergoes a phase change at the LCST. PNIPAM is hydrophilic at temperatures below the LCST, but aggregation occurs at temperatures above the LCST when PNIPAM becomes hydrophobic [14,15]. The change in the LCST of PNIPAM depends on the ions present in the solution. GGoollddnnanaonroordosd(sGR(Gs)Rhsa)vehadveemodnesmtroatnesdtrgarteeadt pgorteeanttiaploftoernutsiaelinfodrruugsdeeliinverdyraungd pdheloivtoetrhyermanadl tphheoratoptyh(ePrTmTa)l[1th8e,1r9a]pSyp(hPeTriTca) l[g1o8l,1d9n]aSnpohpearritciacllegso(AlduNnaPnso) phaarvteicalelisgh(At aubNsoPrsp)thioanvreaangleigohft4a0b0–so60rp0tniomn; hraonwgeevoefr,4v0e0r–y60li0ttnlemo;fhtohwe elivgehrt, vinertyhilsitrtlaenogfetihsealbiglehttoinpathsisstrharnogueghis tahbelesktoinp, athssusthtrhoeuirghPTthTeesffkeicnt, itshuvesrtyheloirwP[T2T0]e. fIfnecctoins tvraersyt, lGoRws[h2a0v].eInthceounntriaqsute, GopRtsichaalvperothpeerutineisquofe sotprotincgallipgrhotpaebrtsioerspotifosntraonndg hliegahtteambsiossrpiotnioinnatnhde hveisaitbelme–insseiaorn-iinnfrtahreevdis(iNblIeR–)nreaanrg-ienf(r7a5r0e–d1(0N00IRn)mra)ndgeep(e7n5d0–in10g0o0nnmth)eidrespieznedainndg aosnptehcet irrastiioze[2a1n–d23a]s.pTehcterGatRios a[2re1−d2e3s]i.gTnheedGtoRasbasroerbdelisgighnt eadt 8t0o8anbmso,rabwligahvet laetn8g0th nthmat, ahawsahvigelhenskgitnh ptheantehtraastihoing[h24sk].inHpoewneevtrear,tiGoRns[2a4re].hHigohwlyevcyetro, tGoRxiscadrueehtiogthhlye hcyextoatdoexciycldtruime etothtyhleahmemxaodneicuymltrbirmomethidyel (aCmTmAoBn) ipurmesebnrot monidtehe(CirTsAuBrf)apcer,eswehnitcohnisthuesierdsutorfamcae,inwtahiinchdiisspuesresdiotno[m25a,2in6t]a. inLodwispcoernscieonntr[2a5ti,o2n6]s. oLfoCwTcAoBnciennctrealltsiodnos nofotCaTffAeBct icnelclegllrsodwothn,obtuatffheicgthceclolngcreonwtrtaht,iobnust chaiughseccoenllcemntermatbiorannsecaduasme acgeell, lmeaedminbgratnoecedlalmdeaagteh, [le2a7d].inTog otovecrecllodmeeatthhi[s2c7y].toTtooxoivceitryc,oomtheetrhsitsucdyiteosthoaxviceituys,eodthpeorlsytmuderiess[2h8a,v2e9]uasnedd pphoolysmpheorlsip[2id8,m29o]leacnudlepsh[o30sp] htoocliopaitdthmeosluecrfualcees o[3f 0G]Rtos. cIonatthtehperseusernfatcsetuodf yG, sRtsa.bIinlittyhies pmraeisnetnatinsetuddbyy, csotaabtiinligtythisemsuarinfataceinoefdthbey GcoRastiwngiththPeNsuIPrfAaMce otof trhede uGcResthweitthoxPicNitIyP.AFMigutorer1edilulucesttrhaetetsotxhiceitsyy.nFtihgeusrise p1riolcluesstsrfaotersththeefinsyanl tchoemsipslepxro(PceNssIPfAorMt/hGeRf-iDnaOl Xc)omanpdletxhe(PreNleIPasAeMof/GthRe-DanOtiXca)nacnedr dthruegredloeaxsoeruobficthine (aDnOticXa)nfcreormdtrhuegcdoomxoprouubnidcinun(DdeOrXN)IfRrolmasethr eircroadmiaptoiounn.d under NIR laser irradiation
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